A large number of anti-aging skin care ingredients are phenolic in nature. Many of these function as anti-oxidants or skin illuminating ingredients, and the free hydroxyl groups are key to the redox activity of these species. Unfortunately, many of these materials have physical properties that are not well-suited for use as cosmetic ingredients. For example, they tend to have minimal solubility in most cosmetic solvents (both oils and water) and can be unstable in a cosmetic formulation (particularly towards oxidation). Derivatization of the phenolic groups can stabilize these materials. However, these derivatives must be readily removable under physiological conditions to liberate the phenolic groups and afford the desired anti-aging activity.
One useful method for derivatization of hydroxyl or carboxyl-containing materials is to prepare esters of these materials. The usefulness of this approach often depends upon the ability of enzymes in the skin to hydrolyze these esters to liberate the parent active ingredient. This strategy is effective for the derivatization of many active ingredients containing aliphatic, alicyclic, or alkaryl alcohols, but esters derived from phenols are often refractive or only slowly reactive towards enzymatic hydrolysis. As described in US Patent Application 2012/0059056 A1, progress in this area has been greatly advanced by the surprising discovery that carbonate esters are easily hydrolyzed in the presence of skin enzymes.
Hydroxytyrosol is a highly active and naturally occurring antioxidant of much interest as a stabilizer and anti-aging ingredient in cosmetic formulations, but the three polar hydroxyl groups make its compatibility with typical lipophilic skin care vehicles very poor. Moreover, even if a suitable vehicle could be found, its ease of air oxidation is a further challenge that limits its use for these applications.
It is desirable to obtain an anti-aging compound that is stable to oxidation, can be hydrolyzed to revert to an active compound, and is soluble in lipophilic vehicles or carriers that are often used in personal care compositions. It would also be desirable to provide a practical synthesis of such a compound from commercially available starting materials with high yields and minimal formation of by-products. A desirable synthesis would be suitable for scale-up to kilogram or larger quantities.